Staszewska-Woolley J, Woodman O L
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Eur J Pharmacol. 1991 Apr 10;196(1):9-14. doi: 10.1016/0014-2999(91)90402-c.
Bradykinin (BK, 0.05 micrograms/kg) or glyceryl trinitrite (5 micrograms/kg) injected into the left circumflex coronary artery of anaesthetized, open-chest greyhounds, caused pronounced increases in large coronary artery diameter (CD) and coronary blood flow (CBF), whereas des-Arg9-BK (0.05-0.3 micrograms/kg), a selective bradykinin B1 agonist, dose dependently elevated CBF but had little effect on CD. BK-induced increases in CD and CBF were not affected by the intracoronary infusion of a selective B1 receptor antagonist, des-Arg9-[Leu8]BK (40 micrograms/min), but were significantly reduced by the infusion of a selective B2 receptor antagonist, D-Arg0-[Hyp3,Thi5,8,D-Phe7] BK (10-12 micrograms/min). The antagonism was reversible and specific for BK since responses to glyceryl trinitrate were not affected. Bilateral vagotomy (n = 3) or autonomic blockade with atropine (0.1 mg/kg i.v.) and propranolol (1 mg/kg i.v.) (n = 5) resulted in significant attenuation of BK-induced increases in CBF but not that of CD. It is concluded that BK is a potent dilator of both conductance and resistance coronary vessels in anaesthetized greyhounds. The dilatation of conductance vessels appears to involve a selective interaction with B2 receptors, while BK-induced increase in CBF may be mediated by both B1 and B2 receptors and involve participation of neuroreflex mechanisms.
将缓激肽(BK,0.05微克/千克)或三硝酸甘油酯(5微克/千克)注入麻醉开胸的灵缇犬左旋冠状动脉,可使大冠状动脉直径(CD)和冠状动脉血流量(CBF)显著增加,而选择性缓激肽B1激动剂去-精氨酸9-缓激肽(des-Arg9-BK,0.05 - 0.3微克/千克)虽剂量依赖性地增加CBF,但对CD影响甚微。BK诱导的CD和CBF增加不受冠状动脉内注入选择性B1受体拮抗剂去-精氨酸9-[亮氨酸8]缓激肽(des-Arg9-[Leu8]BK,40微克/分钟)的影响,但被注入选择性B2受体拮抗剂D-精氨酸0-[Hyp3,Thi5,8,D-苯丙氨酸7]缓激肽(D-Arg0-[Hyp3,Thi5,8,D-Phe7]BK,10 - 12微克/分钟)显著降低。这种拮抗作用是可逆的且对BK具有特异性,因为对三硝酸甘油酯的反应不受影响。双侧迷走神经切断术(n = 3)或用阿托品(0.1毫克/千克静脉注射)和普萘洛尔(1毫克/千克静脉注射)进行自主神经阻滞(n = 5)导致BK诱导的CBF增加显著减弱,但对CD增加无影响。结论是,BK是麻醉灵缇犬中传导性和阻力性冠状动脉血管的强效扩张剂。传导性血管的扩张似乎涉及与B2受体的选择性相互作用,而BK诱导的CBF增加可能由B1和B2受体介导,并涉及神经反射机制的参与。